Five high school freshmen: Olivia White (Bridgit Mendler), Mohini "Mo" Banjaree (Naomi Scott), Charles "Charlie" Delgado (Blake Michael), Stella Yamada (Hayley Kiyoko), and Wendell "Wen" Gifford (Adam Hicks) all meet after ending up in detention for different reasons. While there, they tap out a beat and play instruments, and Olivia sings "Turn Up the Music". Miss Reznick (Tisha Campbell-Martin), the music teacher, said that they would make a great band. She also mentions a music show "Rising Star". Mudslide Crush, a popular band were also entering so they passed as they wouldn't have a shot.

The next day, the group eats at their local pizzeria and they talked about Miss Reznick's words. The band forms with Olivia as lead vocalist, Stella as lead guitarist, Mo as bass guitarist, Wen as keyboardist, and Charlie as drummer,[6] but they are unable to choose a band name. At school, Olivia gets cornered by Ray Beech (Chris Brochu), lead singer of a rival band, Mudslide Crush, who begins questioning and bullying her. The rest of the band intervenes and Stella spits lemonade onto Ray. Ray refers to Stella as "lemonade mouth" and Olivia, the narrator, states: "And that is how we got our band name."

The band is later shocked to see that the unique lemonade machine, "Mel's Organic Lemonade", is scheduled for removal. The school principal, Stanley Brenengen (Christopher McDonald) moved all extracurricular activities to the school basement to make room for a new gymnasium. When Mo sees her boyfriend, Scott Picket (Nick Roux), the guitarist of Mudslide Crush, heavily flirting with another girl, she is devastated and leaves him. Meanwhile, Olivia and Wen meet to work on a song together and bond. At the Halloween bash, Lemonade Mouth performs "Determinate." After the performance, Stella makes a speech opposing Brenengen's decisions and encouraging self-expression to the supportive crowd. Angered, Principal Brenengen shuts them down and calls them to his office the next day. He compliments their talent as a band, but forbids them from playing at school again. The next day, the band sees posters and banners all around the school supporting Lemonade Mouth, which raises their spirits. They also discover that "Determinate" is playing on the local radio. Shortly after, however, things go downhill: Mo gets sick, Charlie breaks his fingers when he angrily closes the cabinet where he keeps his drumsticks, Wen injures his eye when he loses control of a picture frame after he becomes shocked at the news of his father when he asked him to be his best man in his marriage, and Olivia loses her voice after arguing with Wen for complaining about his father's girlfriend.

Stella calls the band to the school, where she is protesting the removal of the lemonade machine. The group gets into a heated argument with one another and fight with the men removing the lemonade machine. Police arrive and they are brought to a holding cell to wait for their parents. After contemplating giving up, the band agrees to stick together and perform at Rising Star (an upcoming "battle of the bands" where the winner wins a record deal), even though they realize that they will not win the competition.

At Rising Star, Mudslide Crush performs "Don't Ya Wish U Were Us". Lemonade Mouth takes the stage and tries to perform "Determinate," but only Stella is able to play, due to their injuries. Discouraged, they start to leave. The audience then begins to sing "Determinate" together in support of the band. Fed up with Ray, Scott leaves Mudslide Crush and plays with Stella, joining Lemonade Mouth as they stand together in tears, watching the audience sing for them. In narration, Olivia reveals that although they did not win the competition, they won something bigger that night. Things start patching up again for the band: Mo and Scott get back together; Charlie, who had previously liked Mo, accepts this and decides to aim his attention at a girl who likes him; Stella and her mother become close again, and Wen accepts his new stepmother.

At Wen's father's wedding, the man sitting next to Stella tells her that he was in a band himself and now runs an organic lemonade company that has recently become very successful. Stella recognizes him as Mel, and he agrees to donate a music hall for Ms. Reznik and everything works out after all. Mr Brenigan confesses to Ms Reznik that he was once a rebellious teen like Stella, and the two adults become flirtatious. Olivia mails the entire story to her father, whom she has not seen in years because he is in prison. The standard edition of the film closes with Lemonade Mouth performing "Breakthrough" at Madison Square Garden, with Scott as their new additional guitarist. The extended edition includes an interview with Moxie Morris on "All Things Musical", in which Mo and Scott's relationship is nearly exposed by Moxie in front of Mo's father, but they are saved by Olivia, who announces that she and Wen are the ones dating. Afterwards, the band performs "Livin On A High Wire".

The movie was filmed in Albuquerque, New Mexico.[9] The names of eight characters in the book were changed for the film: the character of "Olivia Whitehead" was shortened to "Olivia White", "Wendel Gifford" changed by one letter to "Wendell Gifford", "Stella Penn" changed to "Stella Yamada", "Mohini Banerjee" changed to "Mohini Banjaree", and "Charlie Hirsh" changed to "Charlie Delgado". Casting was announced in August 2010.[10]

Family-oriented reviewers at Common Sense Media praised the film for its themes of honesty, empowerment, overcoming adversity, self-expression, standing up for what one believes in, and for its emphasis on the importance of the arts and of friendship and family.[2] Other reviews were not so kind, with some critics claiming that Lemonade Mouth is a "typically innocuous Disney Channel flick" that is a "hopelessly dumbed-down endeavor." The film holds an 6.7 rating, making "Fair" (based on 17 votes) on TV.com.[11]

Lemonade Mouth was watched by 5.7 million viewers on its premiere night.[12] ranking as the No. 1 TV Telecast among Kids 7–11 (2.3 million/9.4 rating) and Teens (2.1 million/8.5 rating), and cable's No. 1 original movie of 2011 among Total Viewers.[13] With DVR viewing included, its total was 7.1 million viewers.[14]

A local premiere was held in the author Mark Peter Hughes's town of Wayland, Massachusetts. It was broadcast live by the town public access station, WayCAM.TV, by local students. The premiere broadcast was directed and produced by technical student Jonah Camiel.[5]

In 2011, the author of Lemonade Mouth said that he has been working on a sequel.[16] Also, Blake Michael has said: "It's all up to the fans, it's in their hands. If people enjoy it and they love it and they want more, they'll get it. I think Disney is just a great organization in general and they're always one step ahead of the game. So you never really know what's gonna happen."[17] On June 15, 2011, it was announced during the 2011 Licensing International Expo that Lemonade Mouth 2 is in the works.[18]

On April 6, 2012, Chris Brochu announced on his Twitter account, that the sequel was no longer going into production.[19] In interviews with Kidzworld Media and BSCKids in May 2012, Bridgit Mendler also confirmed that a sequel would not be produced, noting that "they (Disney) tried to figure something out for a sequel, but everyone at Disney felt like the movie had completed its story in the first movie."[20][21]